| 摘要(英) |
Liver X receptors are important modulators of lipid metabolism and inflammatory response. Previously our laboratory had found that the three LXR agonists, such as T0901317, GW3965 and ATI-111, acted slightly differently on the expression of LXR and other related genes, such as CD11, RXRα, SREBP-1c, resistin, MCP-1, and CCL5 in human U937 monocyte and macrophage. We herein studied whether all three LXR agonists differentially affected mRNA expression of LXR and the above genes during the 4-day period of U937 monocyte differentiation to macrophage induced by phorbol 12-myristate 13-acetate (PMA). First, CD11a, b, and c, LXRβ, RXRα, MCP-1, and CCL5 genes expressed higher during the differentiation, while LXRα, SREBP-1c and resistin gene expression declined. Second, T0901317, GW3965, and ATI-111 alone stimulated the expression of LXRα, SREBP-1c mRNAs, and decreased levels of MCP-1 mRNA, and unaltered levels of CD11, LXRβ, RXRα, resistin, and CCL5 mRNAs after 2 and 4 days of treatment. In the presence of PMA, T0901317 enhanced the PMA-increased levels of CD11b, LXRβ, and CCL5 mRNAs and the PMA-decreased levels of resistin mRNA. However, it blocked the PMA-decreased levels of LXRα and SREBP-1c mRNAs and the PMA-increased levels of MCP-1 mRNA, and unaltered PMA-increased levels of CD11a, CD11c, and RXRα mRNAs. Similar effects of GW3965 and ATI-111 to T0901317 on the PMA-altered levels of LXRα, LXRβ, RXRα, SREBP-1c, resistin, MCP-1 and CCL5 mRNAs were observed, except that GW3965 enhanced the PMA-increased expression of CD11a and CD11c mRNAs and that ATI-111 enhanced the PMA-increased expression of CD11c mRNA. These data suggest that the effect of LXR agonist on gene expression during the differentiation of monocytes into macrophages varies with the types of genes and associates with the process of differentiation. Results of the study may help clarify the different magnitudes of actions of different LXR agonists on differentiation of U937 monocytes into macrophages, lipid metabolism and inflammation. |
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